The invention relates to a method for removing leukocytes from a leukocyte-containing suspension and particularly from blood-derived suspensions. The invention also relates to a filter unit construction which can be used in the above method.
Leukocytes in transfused blood are in most cases not only superfluous but often detrimental. Leukocytes in the blood have been found to cause non-hemolytic febrile reactions and alloimmunization as well as to harbor viruses.
Donated blood can be used without prior treatment (xe2x80x9cwhole bloodxe2x80x9d), or, more frequently, is processed to produce a red cell or platelet concentrate. Various methods have been developed to remove leukocytes from these blood products, the most popular being filtration methods.
EP 155003 (to Asahi) and U.S. Pat. No. 4,925,572 (to Pall) describe filtration methods using fibrous, non-woven media to capture the leukocytes as the blood suspension is passed through them. A leukocyte removal rate of over 98% can be obtained using these methods. The disadvantage of these methods is that the filter units used in them must be composed of many layers of filter media in order to reduce leukocyte counts efficiently while at the same time providing a reasonable flow rate. This makes industrial assembly cumbersome and expensive.
An alternate method of leukocyte filtration has been described in European Patent Application EP 406485 (to NPBI Netherlands). This method uses continuous porous membranes for the filtration process instead of fibers. Using cellulose acetate, an exemplary material as described in the above application, results in over 35% of leukocytes remaining in the blood filtrate, as can be seen in FIG. 9. Thus, the above method resulted in a leukocyte removal of less than 65% as compared to greater than 98% for conventional methods. The authors of the above application came to the conclusion that a series of stacked membranes having decreasing pore size in the blood flow direction (xe2x80x98asymmetric filterxe2x80x99) showed a higher leukocyte removal capacity than membranes of uniform pore size. However, only a 25% leukocyte removal was obtained with this xe2x80x98asymmetricxe2x80x99 filter, which contained a series of 8 membranes (FIG. 8). The filtration method described in the above application is therefore not useful for the purpose of leukocyte removal from blood products.
Other recent patents have described the use of polyvinylidene fluoride and polyvinyl formal membranes for use in leukocyte removal (see e.g. WO 89/02304).
Leukocyte removal by commercial nitrocellulose membranes has been described in U.S. Pat. Nos. 5,820,755 and 5,707,526 (Kraus et al.). A leukocyte removal of 97-99% was obtained using filters including nitrocellulose membranes in a main filter layer, and an upstream pre-filter as illustrated in FIG. 1. However, since the membrane is more efficient in leukocyte capture than the pre-filter media, the leukocytes form a concentrated xe2x80x9ccakexe2x80x9d in the membrane layer and further filtration causes some of the leukocytes to leak out as illustrated in the figure. Such leakage may make filtration quality unacceptable.
There is provided in accordance with one embodiment of the invention a filter unit for a blood-derived suspension containing leukocytes, the filter unit comprising: a main filter for blocking the leukocytes comprising at least one membrane layer, and a post-filter for preventing leakage of the leukocytes comprising at least one layer wherein the post-filter is placed downstream of said main filter and has a median pore size higher than the median pore size of said main-filter.
Further in accordance with an embodiment of the invention the main filter comprises at least one nitrocellulose membrane layer or nylon membrane layer which may be modified by a surface treatment reaction and has a median pore size in the range of 5-15 microns.
Further in accordance with an embodiment of the invention the post-filter comprises at least one non-woven polymer fabric layer and/or membrane layer.
Further in accordance with an embodiment of the invention the filter unit comprising at least one pre-filter placed upstream of the main filter and having a median pore size higher than the median pore size of the main filter.
There is thus provided in accordance with an embodiment of the invention a method for removing leukocytes from a blood-derived suspension comprising leukocytes, comprising the step of: passing the suspension through a filter unit including main-filter for blocking leukocytes and post-filter located downstream of the main-filter.